Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Japan.
Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Japan.
Gynecol Oncol. 2016 Apr;141(1):49-56. doi: 10.1016/j.ygyno.2016.02.027.
Prognoses of ovarian cancer (OC) have improved with the paclitaxel-carboplatin regimen. However, it remains unclear which cases exhibit a genuine benefit from taxane or from platinum. We aimed to predict taxane and platinum sensitivity in OC via gene expression.
We identified differentially expressed genes in responsive and resistant cases from advanced OC biopsy expression dataset GSE15622, containing responses to paclitaxel or carboplatin monotherapy. These genes generated a scoring system for prediction of drug response by applying single-sample gene set enrichment analysis. Discriminative metrics termed the T-score and C-score were derived.
High C-score levels were significant in responders compared to non-responders in a separate cisplatin treatment dataset (GSE18864, p=0.043). High C-score groups also had significantly better progression-free survival in three OC datasets (The Cancer Genome Atlas, TCGA: p=0.02; GSE9891: p=0.03; GSE30161: p=0.001). In two additional datasets of advanced OC, high T-scores could associate taxane and platinum regimens with better survival than non-taxane and platinum regimens (GSE9891: p<0.0001; GSE3149: p=0.045), whereas in cases with low T-scores, different chemotherapeutic regimens did not result in a significant difference. Assessing TCGA and GSE9891, T-scores were elevated in the C1/Mesenchymal subtype, whereas C-scores were elevated in the C5/Proliferative subtype and were lower in the C1/Mesenchymal subtype (p<0.0001, respectively). C- and T-scores negatively correlated with each other, suggesting complementary roles of taxane and platinum.
Our proposal and finding of a scoring system that could predict platinum or taxane response could be useful to develop individualized treatments to ovarian cancer.
紫杉醇-卡铂方案改善了卵巢癌（OC）的预后。然而，目前尚不清楚哪些病例从紫杉烷或铂类中真正受益。我们旨在通过基因表达预测 OC 中紫杉烷和铂类的敏感性。
我们从包含紫杉醇或卡铂单药治疗反应的晚期 OC 活检表达数据集 GSE15622 中鉴定了反应性和耐药性病例中的差异表达基因。通过应用单样本基因集富集分析，这些基因生成了一个用于预测药物反应的评分系统。衍生出了称为 T 评分和 C 评分的判别指标。
在单独的顺铂治疗数据集（GSE18864，p=0.043）中，高 C 评分水平在反应者中与非反应者相比具有显著意义。在三个 OC 数据集（癌症基因组图谱，TCGA：p=0.02；GSE9891：p=0.03；GSE30161：p=0.001）中，高 C 评分组的无进展生存期也显著更好。在另外两个晚期 OC 数据集，高 T 评分可以将紫杉烷和铂类方案与非紫杉烷和铂类方案与更好的生存相关联（GSE9891：p<0.0001；GSE3149：p=0.045），而在 T 评分较低的情况下，不同的化疗方案并没有导致显著差异。评估 TCGA 和 GSE9891，T 评分在 C1/间充质亚型中升高，而 C 评分在 C5/增殖亚型中升高，在 C1/间充质亚型中降低（分别为 p<0.0001）。C 评分和 T 评分相互负相关，提示紫杉烷和铂类具有互补作用。
我们提出并发现了一种可以预测铂类或紫杉烷反应的评分系统，这可能有助于为卵巢癌开发个体化治疗。
